Data sets on CB concentrations in fish-eating mammals from five laboratories were combined to test and refine a pharmacokinetic model. Clear differences in PCB patterns were observed between species. The ability to metabolize chlorobiphenyl (CB) congeners with vicinal H-atoms only in the ortho- and meta-positions and with one ortho-chlorine substituent generally increased in the order otter < cetaceans (harbor porpoise, common dolphin) < phocid seals (harbor and grey seal), but the metabolism of congeners with vicinal H-atoms in the meta- and para-positions and with two ortho-chlorines increased in the order cetaceans < seals < otter. Both categories of congeners are probably metabolized by different families of cytochrome P450 (1A and 2B) of which levels apparently differed between the cetaceans, the pinnipeds, and the otter. Within-species CB patterns differed in a concentration-dependent manner. The induction of cytochrome P450 enzymes offers the most likely explanation for this phenomenon, but starvation could have a similar effect on occasion.

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This retrospective study documents that the implementation of targeted therapy has resulted in significantly improved treatment rates and overall survival in a complete national cohort of treated mRCC patients.

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